2. Academic Validation
  3. In vivo pharmacokinetic and pharmacodynamic profiles of orbifloxacin against Staphylococcus aureus in a neutropenic murine thigh infection model

In vivo pharmacokinetic and pharmacodynamic profiles of orbifloxacin against Staphylococcus aureus in a neutropenic murine thigh infection model

  • BMC Vet Res. 2025 Aug 29;21(1):531. doi: 10.1186/s12917-025-04974-8.
Long-Gen Zhong 1 2,  Si-Jia Tang 1 2,  Liu-Yan Liang 1 2,  Xin Yao 1 2,  Li-Wen Sun 1 2,  Jian Sun 1 2,  Xiao-Ping Liao 1 2,  Yu-Feng Zhou 3 4
Affiliations

Affiliations

  • 1 State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  • 2 Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  • 3 State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China. [email protected].
  • 4 Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China. [email protected].
PMID: 40883777 DOI: 10.1186/s12917-025-04974-8
Abstract

Background: Orbifloxacin is a broad-spectrum fluoroquinolone Antibiotic developed for veterinary use in the treatment of skin and soft tissue infections, as well as respiratory tract infections. This study aimed to define the pharmacokinetic/pharmacodynamic (PK/PD) indices and target exposures associated with Antibacterial activity, thereby providing a rational framework for the development and optimization of orbifloxacin dosing regimens in the treatment of Staphylococcus aureus infections.

Results: The PK profiles and PK/PD relationship of orbifloxacin against S. aureus were investigated using a neutropenic murine thigh Infection model with multiple dosing regimens. Orbifloxacin exhibited a short-duration post-antibiotic effect (PAE; 0.12–2.45 h) and a longer post-antibiotic sub-MIC effect (PA-SME; 2.13–5.29 h) against S. aureus. The dose-response analysis indicated that the area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) ratio over 24 h (AUC24h/MIC) was a strong PK/PD index predictive of Antibacterial efficacy (R² >0.98). AUC24h/MIC targets of 33.78–37.79 h, 53.30–61.56 h, 88.59–98.35 h, and 179.43–217.47 h were required to achieve bacteriostatic, 1-log10, 2-log10, and 3-log10 Bacterial reductions, respectively.

Conclusions: The results confirm that AUC24h/MIC is an appropriate PK/PD index for predicting Antibacterial efficacy and establish target exposure values required to achieve various levels of Bacterial kill.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12917-025-04974-8.

Keywords

Staphylococcus aureus; Orbifloxacin; PK profile; PK/PD.

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